N,2-dimethylpropan-2-amine

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of N,2-dimethylpropan-2-amine (16.0 mg, 0.189 mmol) and triethylamine (19.1 mg, 0.189 mmol) in DCM (1.5 mL), cooled to 0° C., was added triphosgene (19.0 mg, 0.0640 mmol), followed by additional triethylamine (28.7 mg, 0.284 mmol). After 10 minutes of stirring at 0° C., the ice bath was removed and the reaction was allowed to warm to ambient temperature. After 45 minutes at ambient temperature the reaction was cooled to 0° C. prior to the introduction of a chilled (0° C.), DCM (1 mL) solution of triethylamine (19.1 mg, 0.189 mmol) and N-(3,5-difluorobenzyl)-2-{[(4S)-3-methyl-2,5-dioxo-1′,3′-dihydrospiro[imidazolidine-4,2′-inden]-5′-yl]amino}-2-oxoethanaminium chloride (85.0 mg, 0.189 mmol, Intermediate 1). The ice bath was allowed to slowly melt overnight as the reaction warmed to ambient temperature. The reaction was then diluted with EtOAc (50 mL) and then washed with 1M HCl (50 mL, twice), half-saturated brine (50 mL) and saturated brine (50 mL). After drying over sodium sulfate, filtration and concentration in vacuo gave a residue which was applied to a silica gel column for purification, eluting with DCM:MeOH—99:1 to 90:10. The product containing factions were pooled and concentrated in vacuo to give a residue that was not of sufficient purity. This residue was applied to a second silica gel column for purification, eluting with DCM:MeOH—99:1 to 95:5. The product containing factions were pooled and concentrated in vacuo to give 30 mg of the title compound. MS: m/z=550 (M+23(Na+)). HRMS: m/z=528.2428; calculated m/z=528.2417 for C27H32N5O4F2. the ice bath was removed to warm to ambient temperature After 45 minutes at ambient temperature the reaction was cooled to 0° C. warmed to ambient temperature washed with 1M HCl (50 mL After drying over sodium sulfate, filtration and concentration in vacuo gave a residue which was applied to a silica gel column for purification eluting with DCM The product containing factions concentrated in vacuo to give a residue that This residue was applied to a second silica gel column for purification eluting with DCM The product containing factions concentrated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-Fluorobenzoyl chloride was reacted with N-methyl-N-tert-butylamine using General Method E1 or E2 to produce N-methyl-N-(tert-butyl)-3-fluorobenzamide. This compound was used in General Method A to prepare the title compound. Kugelrohr distillation afforded 12.07 g of analytically pure desired material. m.p. 32-35° C.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-Fluorobenzoyl chloride was reacted with N-methyl-N-tert-butylamine using General Method E1 or E2 to produce N-methyl-N-(tert-butyl)-3-fluorobenzamide. This compound was used in General Method A to prepare the title compound. Kugelrohr distillation afforded 12.07 g of analytically pure desired material. m.p. 32°-35° C.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-Fluorobenzoyl chloride was reacted with N-methyl-N-tert-butylamine using General Method E1 or E2 to produce N-methyl-N-(tert-butyl)-3-fluorobenzamide. This compound was used in General Method A to prepare the title compound. Kugelrohr distillation afforded 12.07 g of analytically pure desired material. m.p. 32-35° C.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-Fluorobenzoyl chloride was reacted with N-methyl-N-tert-butylamine using General Method E1 or E2 to produce N-methyl-N-(tert-butyl)-3-fluorobenzamide. This compound was used in General Method A to prepare the title compound. Kugelrohr distillation afforded 12.07 g of analytically pure desired material. m.p. 32°-35° C.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of N-methyl-tert-butylamine (2.0 g, 22.9 mmol) in acetone (25 mL) was slowly added 1,3-propane sultone (2.72 g, 21.8 mmol). The mixture was stirred at reflux for 3 h. The reaction mixture was cooled to room temperature. The solid material was collected by filtration, washed with acetone (2×25 mL). The crude product was suspended in 80% Acetone/EtOH. The suspension was stirred at reflux for 30 seconds. The solid product was collected by filtration, and dried in a vacuum oven (50° C.), to afford compound EN (2.9 g, 65%). 1H NMR (DMSO, 500 MHz) δ ppm 9.40 (s (broad), 1H), 3.45 (m, 1H), 2.85 (m, 1H), 2.59 (m, 5H), 1.99 (m, 2H), 1.28 (s, 9H). 13C NMR (DMSO, 125 MHz) δ ppm 63.23, 51.12, 49.73, 34.79, 25.50, 21.72. ES-MS 208 (M−1). at reflux for 3 h The solid material was collected by filtration washed with acetone (2×25 mL) The suspension was stirred at reflux for 30 seconds The solid product was collected by filtration dried in a vacuum oven (50° C.) to afford compound EN (2.9 g, 65%)